Congenital Adrenal Hyperplasia

These results (repeated below) indicate partial 21-hyroxylase deficiency with simple virilization. Testosterone is markedly elevated, confirming the impression of androgen excess. LH and FSH are not elevated, indicating that a pituitary lesion is not driving the testes to produce androgens. The physical features of the testes (small, without masses) do not suggest a primary testicular lesion.

On the other hand, 17-OH-progesterone, the substrate for the 21-hydroxylase reaction in the adrenal, is dramatically elevated and responds appropriately (a two-fold elevation) to ACTH stimulation. Cortisol (the final product of the 21-hydroxylase pathway) is normal and responds only slightly to ACTH stimulation (less than 50% increase).

                                        Patient          Reference
Testosterone (S)                       172 ng/dl          2 - 12
Lutenizing Hormone (LH), basal (S)     1.7 mU/ml              <2 (pre-puberty)
FSH, basal (S)                          <1 mU/ml              <1
17-OH-progesterone
    basal (S)                       11,690 ng/dl            <100
    60 min after ACTH stim (S)      22,000 ng/dl            <250
Cortisol
    basal (S)                            7 ug/dl          5 - 20 (morning)
    after ACTH stimulation (S)          10 ug/dl           2 - 3 x basal

In partial 21-hydroxylase deficiency, 21-hydroxylase activity is reduced, but some cortisol can be made. However, the pituitary has to drive the adrenal hard (by ACTH stimulation) keep cortisol near the normal level. Precursors to the 21-hyroxylase reaction are markedly increased, while the output of the pathway (cortisol) is normal or mildly decreased. In the process, the amount of material coming out of the side reactions in the adrenal (e.g., androgens) is markedly increased and can cause physiological effects.

The adrenal glands respond to the high levels of ACTH with hyperplasia, and a CT or MRI scan of the abdomen will reveal bilaterally and symmetrically enlarged adrenals.

Treatment

Hydrocortisone replacement therapy suppresses the pituitary output of ACTH, allowing the adrenal gland to decrease its metabolic output and normalizing the androgen synthesis rate.

Additional notes

More severe 21-hydroxylase deficiencies may present with electrolyte and volume disturbances resulting from mineralocorticoid deficiency. These patients may require replacement with both glucocorticoids and mineralocorticoids. Treatment requires care because rapid changes in the testosterone level may initiate central (pituitary) puberty. In any case, the patients require pituitary suppression until puberty.